Effect of antiviral drugs and hematopoietic growth factors on in vitro erythropoiesis.
BACKGROUND
The purpose of these studies was to improve our understanding of nucleoside analog, antiviral, drug-induced anemia in HIV infection.


METHODS
Peripheral blood erythroid progenitor cells (BFU-E) from HIV-positive (HIV+) patients and normal donors were compared in methylcellulose cultures with erythropoietin, with and without antiviral drugs, and with and without the hematopoietic growth factors, stem cell factor (SCF), hemin, and interleukin-3 (IL-3).


RESULTS
Normal numbers of BFU-E-derived colonies were observed in cultures from HIV+ patients (mean +/- 1 SD BFU-E/10(5) cells plated: normal = 14.1 +/- 7.9, HIV+ = 17.2 +/- 14.2, p = 0.39). The antiviral drugs zidovudine (AZT), dideoxyinosine (ddI), and didehydrodideoxythymidine (d4T) all inhibited erythroid colonies in HIV+ and normal cultures. AZT was the most erythropoietically inhibitory drug (AZT ID50, mean +/- 1 SD for normal cultures = 2.64 +/- 4.15 microM, for HIV+ cultures = 6.28 +/- 10.79 microM, p = 0.24). Hematologic toxicity was less with ddI and d4T. However, doses of ddI and d4T < or = 10 microM inhibited colony growth in 9/14 and 8/12 cultures, respectively, from HIV+ patients.


CONCLUSIONS
Stem cell factor (SCF), hemin, and interleukin-3 (IL-3) increased colony growth in HIV+ and normal cultures. In control cultures, hematopoietic growth factors added singly increased growth 1.3- to 8-fold. Hematopoietic growth factors increased growth even in cultures containing antiviral drugs. In some instances growth factors restored growth to control levels. SCF, hemin, and IL-3 were most effective when combined.
Weinberg
R S
RS
Polly Annenberg Levee Hematology Center, Mount Sinai School of Medicine, New York, NY 10029, USA.
Chusid
E D
ED
Galperin
Y
Y
Thomson
J C
JC
Cheung
T
T
Sacks
H S
HS
D000328:Adult; D000740:Anemia / Q000209:etiology* / Q000503:physiopathology; D000998:Antiviral Agents / Q000494:pharmacology*; D016022:Case-Control Studies; D015672:Erythroid Precursor Cells / Q000187:drug effects; D004920:Erythropoiesis / Q000187:drug effects*; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged
D000998:Antiviral Agents; D016298:Hematopoietic Cell Growth Factors